Objectif
Interactions between bacteria and their viruses (bacteriophages) have led to the evolution of a wide range of bacterial mechanisms to resist viral infection. The exploitation of such systems has produced true revolutions in biotechnology; firstly, the restriction-modification (RM) enzymes for genetic engineering, and secondly, CRISPR-Cas9 for gene editing. This project aims to unravel the mechanisms and consequences of prokaryotic immune systems that target covalently-modified DNA, such as base methylation, hydroxymethylation and glucosylation. Very little is known about these Type IV restriction enzymes at a mechanistic level, or about their importance to the coevolution of prokaryotic-phage communities. I propose a unique interdisciplinary approach that combines biophysical and single-molecule analysis of enzyme function, nucleoprotein structure determination, prokaryotic evolutionary ecology, and epigenome sequencing, to link the molecular mechanisms of prokaryotic defence to individual, population and community-level phenotypes. This knowledge is vital to a full understanding of how bacterial immunity influences horizontal gene transfer, including the spread of virulence or antimicrobial resistance. In addition, a deeper analysis of enzyme function will support our reengineering of these systems to produce improved restriction enzyme tools for the mapping of eukaryotic epigenetics markers.
Champ scientifique
- medical and health sciencesmedical biotechnologygenetic engineeringgene therapy
- medical and health sciencesbasic medicineimmunology
- natural sciencesbiological sciencesecologyevolutionary ecology
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes
- natural sciencesbiological sciencesgeneticsepigenetics
Mots‑clés
Programme(s)
Thème(s)
Régime de financement
ERC-ADG - Advanced GrantInstitution d’accueil
BS8 1QU Bristol
Royaume-Uni